Heart disease is the leading cause of death in the United States, and as lifespans continue to extend, the incidence of cardiovascular deterioration and heart failure in humans has dramatically increased. With prolonged aging there is significant remodeling within the cellular microenvironment leading to pathological alterations of myocardial tissue structure such as fibrosis and hypertrophy. These alterations largely result from deposition of extracellular matrix (ECM) components that adversely affect the mechanical properties of the tissue and lead to decreased contractile performance. Studying age-related heart failure in genetically tractable models is critical in order to determine what genetic influences and cellular mechanisms result in the decline of cardiac performance with age. Drosophila melanogaster, commonly known as the fruit fly, has been used previously as a model organism for cardiac genetics due to the relative conservation of human genes; however, it is also an ideal model for studying age-induced cardiac decline due to its short life span. The multilayered design of the heart provides a simpler structure in which to study how any age-associated ECM remodeling alters mechanical coupling between layers via modified ECM-costamere-sarcomere mechanotransduction to adversely impact cardiomyocyte contraction. Preliminary data suggests a correlation between ECM remodeling and contraction through reduced diastolic diameter and increased arrhythmicity. Atomic force microscopy (AFM) analysis previously used for measuring passive myocardial stiffness in Drosophila has also identified differences in the stiffness and thickness of the ECM layer between the ventral muscle and underlying cardiomyocytes. From these data, I propose that age-related ECM remodeling, i.e. ECM composition and assembly changes, alters the adhesive cross talk between fly heart layers, leading to distinct genotype-specific cardiomyopathies. I will first [1] examine ECM compositional, structural, and mechanical changes between the ventral and cardiomyocyte muscle layers in Drosophila strains to assess the effect of ECM on age-associated diastolic decline. I then will [2] functionally assess the contribution of major cardiac ECM proteins in mediating cell-ECM adhesion between layers during aging. Using the Drosophila cardiac aging model I hope to gain a better understanding of how in vivo cell integrin-ECM cross-talk affects mechanoelectric coupling of layers within cardiac tissue.